The regulation of expression of rat carcinogen-inducible and constitutive cytochromes P-450 was examined. The tissue specific response to 3- methylcholanthrene (MC) treatment was probed both immunochemically with antibodies to P-450c, and enzymatically by aryl hydrocarbon hydroxylase (AHH) activity. The level of P450c in rat tissue homogenates decreased in the order: liver, nasopharynx, lung, pancreas, kidney. The levels of P-450c and AHH did not correlate, indicating that extrahepatic AHH activity significantly derives from P450 forms other than P-450c, and/or the specific activity of P-450c varies among different tissues. The induction of rat liver microsomal and nuclear envelope P450s by 2-acetylaminofluorene (AAF) and MC was examined. P-450c and P-450d were differentially induced in microsomes and nuclear envelopes by each agent. In addition, the antioxidant butylated hydroxytoluene accentuated AAF induction of P450c. The effect of aging on several testosterone-hydroxylating P-450s was studied. Twenty-four month old rats had elevated levels of P-450a and its associated 7alpha-hydroxylase activity, but lower levels of several other hydroxylase activities. Thus, although P-450 catalyzed activities generally decline with age, expression of individual P-450s are selectively repressed or activated.